The State of Israel
Ministry of Health
Chief Scientist Office
Israeli Medical Abstracts Repository (IMAR)
Research Number:
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300000-7324
Brainstem and impaired consciousness
Marshall Devor, Professor
The Hebrew University of Jerusalem
none
n.a.
Year (Start): 2011 Year (End): 2013
Background: We have discovered a brainstem locus, the MPTA (mesopontine tegmental anesthesia
area), at which microinjection of a minute quantity of GABAA-R-active anesthetics rapidly induces a
transient coma-like (anesthesia-like) state. This observation is incompatible with the widely held
presumption that loss of consciousness is due to the distribution of anesthetic agents throughout the
cerebral cortex with consequent suppression of cortical function by
Research Hypothesis: We hypothesize that, rather than global suppression of GABA transmission, the
transition from wake to unconsciousness in general anesthesia is due to drug action on a specific and
definable neural network. The MPTA is a nodal point in this network.
Aims: The overall objective of this project is to characterize the hypothesized MPTA-related brain
network. Our specific aims were to determine whether the MPTA, via its associated network, plays an
important role in clinical (systemic-induced) general anesthesia.
Methods: Axon-sparing neuron-selective lesions were made in the rat brain by stereotaxically
microinjecting the excitotoxin ibotenic acid into the MPTA and monitoring behavioral outcomes.
Results: MPTA lesions did not cause coma, stupor or even obvious sedation. However, MPTA lesions
did alter the systemic dose of pentobarbital required to induce anesthesia with systemic administration.
Specifically, they shifted the dose-response curve to the right. There was no change in the effective
anesthetic dose of ketamine, a dissociative anesthetic that acts via a different receptor system.
Discussion: The results support the novel architecture that we propose: that systemically administered
GABAA-R-active anesthetics cause the brain to transition from wake to unconsciousness by means of
network action rather than generalized brain suppression. MPTA neurons play a central role in the
network. An essential next step is to identify partner nuclei and their interconnecting pathways.
Conclusions: General anesthesia, as induced by GABAA-R-active anesthetics at least, appears to be an
adaptive function of a specific endogenous network. Characterizing this network may lead to improved
clinical anesthesia, better management of patients with impaired consciousness (e.g. coma) and,
perhaps, new insights into the neural mechanisms underlying consciousness itself.
Key words: anesthesia, arousal, brainstem, brain networks, coma, MPTA
The State of Israel
Ministry of Health
Chief Scientist Office
Israeli Medical Abstracts Repository (IMAR)
Publications associated with the project:
Sukhotinsky, I and Devor, M. Networks for the Modulation of Acute and Chronic Pain. chapter 23
In: Blumenfeld H. and Faingold C. Neuronal Networks in Brain Function, CNS Disorders, and
Therapeutics. Elsevier, New York, 2013, in press.